anxiolytics med chem lecture

Psychotropic Agents

These are drugs that cure mental disorders.

Mental disorders includes abnormal changes in

how a person feels, acts, thinks or perceives

which degrades ability to function in ordinary

life or socialize with others

– Anxiolytic

– Antidepressents

– Antiphycotics

AnxiolyticsDrugs that cause mental clamness

Anxiety

• Anxiety is a normal fear response to stress or threats. It helps us to prepare for a “fight or flight” action

• Too much or unnecessary anxiety can cause stress related disorders ranging from cognitive block to pain and heart palpitations (abnormal heart beat)

Types of Anxiety

• General Anxiety

• Obsessive Compulsive Disorder

• Panic Disorder

• Post Traumatic Stress Disorder

• Specific Phobias

• Social Anxiety

Is anxiety really a disease? Yes

Clinical effects of General Anxiety• Constant worrying or obsession about small or large

concerns • Restlessness and feeling on edge • Fatigue • Difficulty concentrating or your mind "going blank" • Irritability • Muscle tension or muscle aches • Trembling, feeling twitchy or being easily startled • Trouble sleeping • Sweating, nausea or diarrhea • Shortness of breath or rapid heartbeat

Drugs used to treat Anxiety are

1) Benzodiazepines:

– Chordiazepoxide, Clonazepam,

– Alprazolam, Diazepam*, Lorazepam

2) Azapirones - Buspirone

Chlordiazepoxide

• It is a long acting benzodiazepam• It has amnestic, anticonvulsant, anxiolytic, hypnotic

and skeletal muscle relaxant properties• It has an intermediate onset of action (15-30 mins),

with a peak blood level occurring two to four hours after oral administration. It has active metabolite

• Used for the short-term (2–4 weeks) treatment of anxiety

• It’s long term use can cause depression, tolerance and dependence with withdrawal effects similar to alcohol

• MOA- Anxiolytic effect is due to CNS depression caused by stimulation of GABAA receptors

Clonazepam

• It is a intermediate acting benzodiazepam• It has amnestic, anticonvulsant, anxiolytic, hypnotic and

skeletal muscle relaxant properties• It has an intermediate onset of action (15-30 mins), with a

peak blood level occurring one to four hours after oral administration

• Used for the short-term (2-4) treatment of panic disorder (recurring panic attacks- palpitations, shaking and chest pain)

• It’s long term use can cause depression, tolerance and dependence with withdrawal effects similar to alcohol

• MOA- Anxiolytic effect is due to CNS depression caused by stimulation of GABAA receptors

Azapirones: Buspirone

• Azapirones are a class of drugs having both anxiolytics and antipsychotics activity

• Anxiolytic action due to agonism at serotonin (5-HT]) type 1A receptor

• antipsychotics activity is due to antagonism at D2 receptor• It has delayed onset of action but • As potent as diazepam with no tolerance and addictiveness

and no sedative effects, no cognitive or motor impairment• They are very especially safe and effective in elderly

patients• Used limited for mild to moderate anxiety and not useful in

severe cases like panic attack

Thanks

Review

How to they point out SAR of drugs?

Comparative oral doses of various Benzodiazepams

• SAR is developed by analyzing activity of a series of drugs with a small alteration made around a common structure

• These alteration must be planned carefully so that effective comparisons can be made

• We can judge in above compounds that– Substituting Nitrogen decreses activity (1st and 2nd)– Removing hydroxyl group improves activity (1st and 4th)– Having an extra aromatic nitrogen ring is good and

compensates lack of Chlorine in lower ring(6th and 7th)– We know that for diazepams, having electronegative

groups at specific positions is essential for activity and it reflected in these 8 marketed compounds but to include it as a valid SAR we need to compare it’s activity with those structures that lack those electronegative groups

• But these small alteration have big changes in ADME

Assignment

• Refer the given research article and point out SAR of drugs called HDAC inhibitors

• European Journal of Medicinal Chemistry 44 (2009) 1067e1085

• Key skill gained:

• Knowledge on various structural diversity that can be implemented for drug design